Clinicopathologic correlations in leukemia cutis

This clinicopathologic study involved 42 cases of leukemia cutis: 3 of acute lymphocytic leukemia (ALL), 16 of chronic lymphocytic leukemia (CLL), 12 of acute granulocytic leukemia (AGL), 3 of chronic granulocytic leukemia (CGL), 5 of acute monocytic leukemia (AML), and 3 of acute myelomonocytic leukemia (AMML). The clinical appearance of leukemia cutis included papules, macules, plaques, nodules, ecchymoses, palpable purpura, and ulcerative lesions, and these were seen in all types of leukemias. Gingival hypertrophy was seen only in AML or AMML, and erythroderma and bullous lesions of leukemic infiltration were observed only in CLL. Cutaneous leukemic lesions may be concomitant with or preceding the diagnosis of systemic leukemia. Therefore, skin biopsy may be helpful in detecting the leukemia and may facilitate the work-up. Leukemia cutis probably is a dissemination of systemic leukemia to the skin, and the demonstration of leukemia in skin is associated with a very poor prognosis.     

Aleukemic leukemia cutis presenting as benign-appearing exanthema.

Aleukemic leukemia cutis is a rare condition characterized by the infiltration of the skin by leukemic cells before their appearance in the peripheral blood or bone marrow. We report here a 62-year-old seemingly healthy patient who presented with disseminated erythematous maculae. A skin biopsy showed leukemia cutis of monocytic type. No involvement of bone marrow or peripheral blood was found. The patient developed acute monocytic leukemia 7 months later. We present this case to illustrate how leukemia cutis can masquerade as a clinically benign-appearing cutaneous eruption without leukemic changes in blood or bone marrow. To confirm the diagnosis of aleukemic leukemia cutis, immunohistochemistry of the skin lesions as well as a complete staging procedure is necessary.     

Leucemia cutánea aleucémica: presentación de un caso

—The term aleukemic leukemia cutis describes the invasion of the skin by leukemic cells in the absence of peripheral blood and/or bone marrow involvement. Although the pathogenic mechanisms of this disease are still unknown, it is widely recognized its poor prognosis. Most of the reported patients completely developed the hematologic disease (the majority acute granulocytic or monocytic leukemias) in 10-14 months after diagnosis of aleukemic leukemia cutis, and they had a median survival of 22 months.We report on a case of a 77-year-old man with aleukemic leukemia cutis who presented with numerous erythematous to violaceous papulonodular lesions, mainly located on the trunk and head, lack of peripheal blood involvement and very early alterations in the bone marrow aspirate. Inmunohistochemical stains of skin and bone marrow biopsies revealed the infiltration of both tissues by blast cells of monocyte-histiocytic lineage. Our patient presented spontaneous resolution of skin lesions and his hematological disease showed no progression during 9 months after diagnosis, although he did not undergo any treatment.We emphasize the low incidence of association between myelodysplastic syndromes and aleukemic leukemia cutis as well as the surprising spontaneous remission of cutaneous lesions in our patient.     

Aleukemic monocytic leukemia cutis

Aleukemic leukemia cutis is a rare condition in which leukemic cells invade the skin before they appear in peripheral blood or bone marrow specimens. The condition frequently is misdiagnosed as atypical lymphoma. Generally, the diagnosis is made retrospectively, after the leukemic cells appear in peripheral blood or bone marrow samples. Immunohistochemical studies are the primary methods for diagnosis. Prognosis is usually poor. We describe the case of a 75-year-old woman with acute aleukemic monocytic leukemia cutis who developed systemic disease 1 1/2 years after skin involvement.     

Aleukemic leukemia cutis. An unusual presentation of acute myelomonocytic leukemia

A patient with acute myelomonocytic leukemia is reported. He had presented erythroderma and atypical cellular infiltration of the skin 4 months prior to the detection of leukemia in the peripheral blood and bone marrow. Aleukemic leukemia cutis is a rare condition which is characterized by leukemic cells invading the skin prior to the observation of leukemic cells in the peripheral blood. The cases of aleukemic leukemia cutis reported in the literature show little or no conformity in their clinical appearance. Enzyme cytochemistry, immunocytological and electron-microscopic studies are of considerable help in differentiating the cutaneous infiltrates and in establishing early diagnosis. We report herein a patient with erythroderma which regressed spontaneously, whereas microscopic examination of a cutaneous biopsy showed atypical cells infiltrating the dermis. After a period of 3 months, during which the patient remained free of lesions, he showed recurrence of the erythroderma while developing acute myelomonocytic leukemia. We feel this unusual presentation of aleukemic leukemia cutis should be added to the evergrowing list of cutaneous manifestations of leukemia.     

Congenital Leukemia Cutis Preceding Monoblastic Leukemia by 3 Months

Abstract: We report an infant born with a cutaneous nodular eruption and neutropenia. Skin biopsy specimens revealed an immature dermal infiltrate suggestive of leukemia cutis, but repeated peripheral blood and bone marrow examinations failed to demonstrate malignant cells. The eruption resolved spontaneously. At the age of 3 months, a second occurrence of maculopapular skin lesions led to discovery of an acute monoblastic leukemia with (9;11)(p21–22;q23) translocation. Congenital acute leukemia is a rare disease associated with skin infiltration in 25% to 30% of patients. Usually the diagnosis is easily made by peripheral blood examination and/or bone marrow aspirate. However, skin involvement may precede acute leukemia by several weeks. Although very rare, this event must be kept in mind.     

Leukemia cutis resembling a flare-up of psoriasis

Leukemia cutis represents a skin infiltration by leukemic cells. Clinically it can mimic a wide variety of dermatoses. We describe the case of a 64-year-old man with psoriasis who presented with a 4-day history of erythematous, slightly scaly, asymptomatic plaques distributed on the trunk and upper-extremities, and associated asthenia, myalgias, and anorexia. A skin biopsy revealed a leukemic infiltrate. Studies of peripheral blood and bone marrow provided a diagnosis of acute monocytic leukemia. This case report shows the importance of the clinical suspicion for the diagnosis of leukemia.     

有皮肤损害的急性粒细胞白血病1例

患者女 ,30岁 ,病期2年。2年来四肢躯干反复出现丘疹、紫癜、结节 ,伴瘙痒 ,曾多次诊断为湿疹。检查可见周身散在淡红丘疹、结节、水疱及紫癜。左上肢丘疹组织病理检查符合皮肤白血病。骨髓检查及细胞免疫分型确诊急性粒细胞性白血病M2型。     

Acute myelomonocytic leukemia presenting as a benign-appearing cutaneous eruption

Aleukemic leukemia cutis is a rare condition in which patients have skin lesions containing leukemic cells before evidence of leukemia can be detected in the peripheral blood. There are only 23 cases of this phenomenon documented in the English literature. We describe a 62-year-old woman who developed a diffuse, clinically benign-appearing cutaneous eruption, which histologically showed an atypical infiltrate of cells, 4 months before leukemic cells were found in her peripheral blood and the diagnosis of acute myelomonocytic leukemia was made by bone marrow aspiration. This case illustrates the difficulty in diagnosing leukemia cutis from examination of routine histologic sections and the importance of specialized marker studies in determining the cause of an atypical cellular infiltrate of the skin. It also illustrates how leukemia cutis can masquerade as a clinically benign-appearing cutaneous eruption in a seemingly healthy patient with normal blood parameters.     

Aleukemic congenital leukemia cutis

A newborn girl had typical "blueberry muffin" skin lesions, which showed histopathologic features of myelomonocytic leukemia cutis. We could not demonstrate leukemic infiltration of bone marrow in four aspirates. Her course was complicated with primary pulmonary hypertension, which led to death at 7 months of age. We emphasize the persistence of skin lesions in the absence of bone marrow infiltration by leukemia throughout the course of the disease.     

The spectrum of cutaneous disease in leukemias

Cutaneous eruptions are frequent complications in the clinical course of patients with leukemia. Leukemia cutis is occasionally the cause of the eruption, but in many cases the lesions are non-leukemic. We have retrospectively selected all skin biopsies from patients with a computer-coded diagnosis of leukemia seen in the Stanford University Department of Pathology in the last 7 years, and separated these cases into the broad categories of acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL). We also analyzed separately those cases seen in patients treated with bone marrow transplantation from those treated with standard chemotherapy regimens. We found that leukemia cutis was seen frequently as the cause of lesions in patients with CML and CLL. In contrast, a wide variety of lesions were seen in patients with AML, including a greater number of infectious lesions, drug reactions, vasculitis, and lesions secondary to a hemorrhagic diathesis. In the bone marrow transplantation patients, graft vs host disease was usually the cause of skin lesions in those transplanted for CML and ALL, but again those patients with an underlying diagnosis of AML showed a wide variety of lesions including drug reactions, fungal infections and leukemia cutis. Finally, 6% of cases from patients with AML showed intraepidermal blistering disorders of various types, an association that has not been previously reported.     

皮肤白血病1例

患者，男性，22岁。1999年5月出现发热，经血液和骨髓穿刺证实为急性骨髓性白血病M5型（急性单核细胞性白血病）。2000年2月行自身外周血干细胞移植并顺利植活。移植后4个月患者发现前胸部出现紫红色结节、斑块，组织病理为“继发皮肤白血病”，骨髓穿刺和皮损免疫组化诊断为“急性骨髓白血病M5型复发”。经10天化疗，患者皮损减轻。     

Leukemia Cutis Presenting with Fingertip Hypertrophy

Background: Patients with leukemia often manifest cutaneous findings, which include nonspecific lesions and specific leukemic infiltrates termed leukemia cutis. Objective: A case of leukemia cutis involving distal finger pads is reported and literature describing hand involvement of specific leukemic infiltrates is reviewed. Methods and Results: An 80-year-old woman with a 10-year history of chronic lymphocytic leukemia developed painful symmetric tumors of her distal finger pads. Histopathological examination of the biopsy specimen revealed infiltration by neoplastic lymphocytes. Only a few cases of leukemia cutis involving the hands have been reported in the literature, none with this particular presentation. The clinical and histopathologic features of leukemia cutis are reviewed. Conclusion: This case emphasizes the importance of obtaining a biopsy specimen for histopathological examination of any suspicious skin lesion in a patient with leukemia.     

Aleukemic leukemia cutis: juvenile chronic granulocytic leukemia presenting with figurate cutaneous lesions

We report a 3 1/2-year-old girl who developed a figurate cutaneous eruption. Distinctive findings in her skin biopsies, as well as unusual red cell characteristics, in the presence of a normal peripheral smear and bone marrow biopsy, led us to suspect the diagnosis of preleukemic juvenile type chronic granulocytic leukemia. This is the first case we know of in which this diagnosis was suspected prior to abnormal findings in the peripheral smear or bone marrow.     

Value of immunohistochemistry in the diagnosis of leukemia cutis: study of 54 cases using paraffin-section markers

A grave prognosis is usually associated with leukemic skin infiltrates (leukemia cutis). However, some leukemic skin infiltrates are clinically similar to reactive non-leukemic infiltrates in patients with leukemia; thus it is of great importance to distinguish them. Fifty-four cases which were thought clinically to be leukemia cutis underwent immunophenotyping with a panel of nine T, B, monocytic, and macrophage markers using paraffin sections. Immunohistochemistry helped identify 44 cases with leukemia cutis and 10 with reactive infiltrates. In all cases of leukemia cutis, the staining patterns of skin infiltrates were concordant with cell type in the bone marrow. Furthermore, the panel of markers was usually helpful in distinguishing reactive from leukemia infiltrates, especially in cases with chronic lymphatic leukemia. Immunohistochemistry is a valuable adjunct in histopathologic differentiation of skin infiltrates in most cases of leukemia. With formalin-fixed, paraffin-embedded biopsies, we recommend that CD45 (LCA), CD45RO (UCHL-1), CD3, CD20 (L-26), CD43 (Leu-22), CD68 (KP-1), lysozyme, and chloroacetate esterase be considered in cases of systemic leukemia with cutaneous papules and nodules that prove difficult to interpret with routine section.     

以皮疹为首发症状的皮肤白血病一例

报道1例以皮疹为首发症状的急性淋巴细胞白血病.患者女,31岁,胸、腹部红斑伴轻度疼痛3个月就诊.初诊时血常规正常,皮疹活检提示皮肤白血病.1个月后原有红斑上出现瘀点,外周血及骨髓细胞学检查确诊为急性淋巴细胞白血病,腹部皮损免疫组化标记与外周血流式细胞仪分析,证实瘤细胞来源于前驱B淋巴细胞.脑脊液检查示中枢神经系统受累.化疗两次后缓解,1个月后复发,并死于呼吸循环衰竭.     

Clinical and pathological features of myeloid leukemia cutis

BackgroundMyeloid leukemia cutis is the terminology used for cutaneous manifestations of myeloid leukemia.ObjectiveThe purpose of this study was to study the clinical, histopathological and immunohistochemical features of myeloid leukemia cutis.MethodsThis was a retrospective study of clinical and pathological features of 10 patients with myeloid leukemia cutis.ResultsOne patient developed skin lesions before the onset of leukemia, seven patients developed skin infiltration within 4-72 months after the onset of leukemia, and two patients developed skin lesions and systemic leukemia simultaneously. Of these patients, five presented with generalized papules or nodules, and five with localized masses. The biopsy of skin lesions showed a large number of tumor cells within the dermis and subcutaneous fat layer. Immunohistochemical analysis showed strong reactivity to myeloperoxidase (MPO), CD15, CD43 and CD45 (LCA) in most cases. NPM1 (nucleophosmin I) and FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication) mutations were identified in one case. Five patients with acute myelogenous leukemia and one patient with chronic myelomonocytic leukemia died within two months to one year after the onset of skin lesions.Study limitationsThis was a retrospective and small sample study.ConclusionsIn patients with myelogenous leukemia, skin infiltration usually occurs after, but occasionally before, the appearance of hemogram and myelogram abnormalities, and the presence of skin infiltration is often associated with a poor prognosis and short survival time. myeloid leukemia cutis often presents as generalized or localized nodules or masses with characteristic pathological and histochemical findings.     

Differentiation syndrome during ivosidenib treatment with immunohistochemistry showing isocitrate dehydrogenase R132H mutation

We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H-mutated leukemia cutis. A 72-year-old man with IDH1-mutated acute myeloid leukemia (AML), status-post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture-negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase-positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation-specific antibodies such as anti-IDH1 R132H may be useful to help distinguish malignant from non-malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy.     

Chilblain-like leukemia cutis

We present a 6-year-old girl with an 8-month history of fluctuating chilblain-like lesions on the toes. A full blood count showed slight thrombocytopenia and monocytosis. A skin biopsy specimen showed a dense perivascular and superficial dermal cellular infiltrate which was CD3(-), CD43(+), and lysosyme + on immunocytochemistry, suggesting a monocytic origin. Juvenile myelomonocytic leukemia was diagnosed after a bone marrow biopsy and spontaneous marrow colony growth in culture.     

Aleukemia cutis: Clinicopathological and molecular investigation of two cases

We describe two cases of acute myeloid leukemia (AML) who presented with cutaneous manifestations. Leukemia cutis (LC) is the cutaneous presentation of any type of leukemia and occurs in 10% to 15% of patients with AML, but cutaneous infiltration of AML rarely precedes the involvement of the bone marrow or peripheral blood and is called “aleukemia cutis.” Our first case presented with facial skin thickening, a manifestation which is known as lionization and his initial clinical diagnosis was nonspecific allergic reaction. Our second case presented with urticaria-like lesions with the initial clinical and histomorphologic diagnoses of leukocytoclastic vasculitis. Histopathologic examination of skin biopsy specimens in both patients showed diffuse infiltration of the dermis with a monotonous population of intermediate-sized mononuclear cells by open chromatin and promonocytic features. Bone marrow aspiration leukocyte karyotyping showed normal cytogenetics, and molecular investigation revealed mutations of NPM1 and FLT3 genes. Somatic CEBPA gene mutation was negative in both patients. LC as the first manifestation of leukemia is very rare and could result in delayed diagnosis and affect patient prognosis.